PROJECT SUMMARY/ABSTRACT The proposed training fellowship focuses on risks and protective factors in cognitive aging. Increases in the older adult population have resulted concomitant increases in cardiovascular disease (CVD) prevalence, which is a known risk factor for cognitive decline and related cerebrovascular dysfunction. While pharmacological treatment has made substantial advances in reductions of CVD-related events (e.g. heart attack, stroke, lowering cholesterol), there remain considerable gaps in the field?s collective knowledge regarding the impacts of pharmacological treatment on cognitive outcomes. The proposed training plan provides the candidate with additional training beyond that afforded by her Ph.D. program. Emphases afforded by the fellowship, if awarded include (1) coursework in medical and pharmacological aspects of aging (epidemiology, geriatrics, and neuroscience), (2) didactic and hands-on training in the processing of FLAIR and T1 MRI images (for the quantification of white matter disease), and (3) advanced practice with longitudinal data analyses. The candidate is supported by a strong, productive mentoring team with specific expertise in the proposed areas of study. Training is motivated by a research plan that will investigate, in a sample of 20,368 adults aged 60 and older, drawn from the National Alzheimer?s Coordinating Center (NACC). NACC participants along the cognitive continuum (e.g. cognitively normal through dementia) with 2-10 years of follow-up will be included. The NACC database offers an unusually rich source of data in which to investigate these questions because of sample size, longitudinal occasions, broad sampling of individuals, concurrent imaging on a subset of individuals, detailed medication inventories on all participants, and the use of a uniform data set for neuropsychological data collection. The proposed work will investigate the associations between CVD (including both risk factors like hypertension and comorbidities like myocardial infarction), vascular neuropathology (white matter hyperintensities in regions of interest), and trajectories of change in four cognitive domains (Memory, Attention, Executive Function/Processing Speed, and Language). The study will further investigate whether pharmacological treatment (cardiovascular medication) mitigates cognitive decline. Thus, the proposed study has two specific aims: (1) To confirm that participants? level and longitudinal rate of change in CVD is associated with level and rate of change in the four cognitive domains over the subsequent decade; and to further investigate whether pharmacological treatment of CVD moderates that association, and (2) In a subset of participants for whom structural MRI data were collected at baseline, to determine whether baseline indicators of vascular neuropathology mediate the relationship between baseline CVD on level and rate of change in cognition over time.